Raising the Bar in GxP Compliance – Part 9: Mastering Annex 1 for Sterile Manufacturing Excellence.
Welcome to the ninth instalment of Raising the Bar in GxP Compliance, Rephine’s expert-led blog series for QA and regulatory professionals.
In this edition, we unpack the critical updates to EU GMP Annex 1 and what they mean for sterile drug manufacturers. With regulators demanding a deeper commitment to contamination control, aseptic discipline, and quality system maturity, Annex 1 isn’t just a compliance hurdle—it’s a catalyst for operational transformation. Discover how Rephine helps manufacturers not only meet the new standards, but build a future-ready platform for sterile product excellence.
Sterile manufacturing is entering a new era of precision and accountability.
The revised Annex 1 raises the bar for contamination control, demanding integrated, science-driven strategies that span facilities, processes, and people.
Why Annex 1 Matters More Than Ever
The revised EU Annex 1 introduces significant changes for sterile drug manufacturers, emphasising contamination control, risk-based thinking, and the integration of Pharmaceutical Quality Systems (PQS) into aseptic operations.
The new Annex 1, which came into effect in 2023, applies to all manufacturers of sterile medicinal products, regardless of product type or market. It reinforces the importance of a contamination control strategy (CCS) and expands expectations for cleanroom classification, personnel behavior, process validation, and environmental monitoring.
What’s Changed in Annex 1? Key Updates at a Glance
Key updates include:
- Implementation of a documented CCS covering design, operation, monitoring, and continuous improvement.
- More stringent requirements for aseptic process validation, including media fill strategies.
- Enhanced gowning, training, and qualification for cleanroom operators.
- Comprehensive requirements for automated visual inspection and cleanroom technology.
- Increased focus on supply chain controls, cleaning validation, and process risk analysis.
From Procedures to Culture: Meeting the New Annex 1 Standard
These changes demand not only procedural updates but also acultural shift toward proactive quality assurance and integrated risk management.
How Rephine Supports Your Annex 1 Compliance Journey
At Rephine, we support sterile product manufacturers in aligning with Annex 1 expectations
✅ Annex 1 Readiness Assessments: We evaluate your facilities, documentation, and PQS maturity against current Annex 1 clauses and regulator expectations.
✅ CCS Development and Review: Rephine helps you design and document a contamination control strategy tailored to your facility, processes, and microbial risks.
✅ Third-Party GMP Audits: Our audits cover cleanroom operations, aseptic technique, gowning practices, environmental monitoring, and supplier compliance.
✅ Supplier Qualification: We ensure your contract sterilization providers and component suppliers meet Annex 1 requirements through direct audits or report access.
✅ Gap Remediation Planning: We support action planning and revalidation activities needed to achieve full Annex 1 compliance.
Build a Future-Ready Sterile Manufacturing Platform
Navigating Annex 1 isn’t just about satisfying regulators—it’s about building a robust aseptic manufacturing platform for the future. With Rephine as your expert partner, you gain clarity, confidence, and control in your journey toward full Annex 1 alignment.
Dr. Eduard Cayón
CSO (Chief Scientific Officer)
About the Author:
Dr. Eduard Cayón is the Chief Scientific Officer (CSO) at Rephine, a global leader in GxP compliance and quality assurance.
We don’t just deliver audits or consultancy services — we partner with clients at every stage of their quality journey, offering end-to-end solutions that empower confidence and compliance.
With over 25 years of experience, Rephine has built an enviable reputation as the gold standard in the industry operating from four primary locations: Stevenage in the UK, Barcelona in Spain, India, and Shanghai in China.
Dr. Cayón, who holds a Ph.D. in Organic Chemistry, is a deeply experienced pharmaceutical industry consultant and auditor.
He is dedicated to supporting pharmaceutical, biotech, and medical device companies in meeting the highest standards of manufacturing and supply chain integrity.